Glutaric acid Synthesis

The present method, based on a recent publication,8 offers a more convenient synthesis of glutaric acid and its imide, and the method may be readily adapted to a large scale. 

Chiral butyrolactones of type 27 and 28 have substantial value in asymmetric synthesis because they contain readily differentiable difunctional group relationships e.g. 1,5-di-carboxylic acid, 1,4-hydroxy carboxylic acid, 1,6-hydroxy-carboxylic acid, 1,6-diol etc.) that would be difficult to assemble by existing asymmetric condensation and pericyclic processes. Applications of these chiral derivatives of glutaric acid to syntheses of indole, indoline and quinolinone alkaloids are illustrated in Schemes 16-18. 

CTPB. Synthesis. Free Radical-Initiated Prepolymers. There are two principal methods for preparing the free-radical-initiated prepolymers. The first method uses glutaric acid peroxide (2) as the initiator and follows the reaction scheme shown below ... 

Similarly, glutaryl acylase was used as a biocatalyst in the synthesis of amides of glutaric acid derivatives using the acyl donor as the liquid phase in which the undissolved nucleophile was suspended [33]. In another example, immobilized lipase was used in a medium composed solely of substrate to resolve racemic ketoprofen esters via hydrolysis [36]. 

This synthesis has one rather anomalous application, when a-bromo-isobutyric acid (or its ethyl ester) is heated with silver, some tetramethyl-succinic acid is produced in the ordinary way (B., 23, 297 26, 1458). But there also appears trimethylglutaric acid (A., 292, 220). To explain the unexpected formation of this acid, it has been assumed that a portion of the a-bromoisobutyric acid gives up HBr to form methylacrylic acid. This latter then forms j3-bromoisobutyric acid, and the silver withdraws bromine from the a- and /3 acids, whereby the residues unite to tri-methyl-glutaric acid (B., 22, 48, 60). A similar explanation applies to some other syntheses in which tetramethylsuccinic and trimethylglutaric acids appear together. 

Researchers at the biotech company EntreMed, Inc., have recently prepared and tested 2-phthalimidino-glutaric acid analogs of thalidomide and found them to be potent inhibitors of tumor metastasis [28], The key to the success of their synthesis was a resolution via enantioselective ester hydrolysis catalyzed by ChiroCLEC -BL, the CLC form of the protease subtilisin. The authors were able to isolate both enantiomers of the desired product with good optical purity (95% ee) (see Fig. 7). 

Figure 7 Synthesis of 2-phthalimidino-glutaric acid analogs.

JH Shah, GM Swartz, AE Papathanassiu, AM Treston, WE Fogler, JW Madsen, SJ Green. Synthesis and enantiomeric separation of 2-phthalimido-glutaric acid analogues potent inhibitors of tumor metastasis. J Med Chem 42 3012-3017, 1999. 

His main interests include organic chemistry, heterocyclic chemistry (quinolones, dihydropyr-idines, benzimidazoles, benzotriazoles, benzoselenadiazoles, bcnzothiadiazoles, glutaric acids, enol ethers), utilization of heterocyclic compounds in the organic synthesis, and molecular spectroscopy. 

Pig Liver Esterase (PLE). This is the more used car-boxylesterase (carboxylic-ester hydrolase, EC 3.1.1.1, CAS 9016-18-6) which physiologically catalyzes the hydrolysis of carboxylic acid esters to the free acid anion and alcohol. PLE is a serine hydrolase which has been widely used for the preparation of chiral synthons and these applications have been fully reviewed. An active-site model for interpreting and predicting the specificity of the enzyme has been published. In the pioneering studies of the enzyme applications field, PLE was used for the chiral synthesis of mevalonolactone. Prochiral 3-substituted glutaric acid diesters... 

Synthesis from Propane.—The constitution of glutaric acid as i 5-pentan-di-oic acid is proven by its synthesis from 1-3-di-cyano propane which in turn is prepared from 1-3-di-brom propane, as follows ... 

From Aceto-acetic Ester.—Glutaric acid may also be made by either the aceto-acetic ester synthesis or by the malonic ester synthesis as follows,... 

Adipic Acid—Of the di-carboxy acids which contain more than three carbon groups between the two carboxyls we need only mention two. Adipic acid, like glutaric acid, is found in the juice of the sugar beet. Its systematic name is 1-6 hexan-di-oic acid and its formula is, HOOC CH2—CH2—CH2—CH2—COOH. It may be synthesized by the same general methods as those described in connection with glutaric acid. The constitution of adipic acid has been proven by the following synthesis from /8-iodo propicnic acid, in which two molecules of the acid are condensed by means of silver. 

Kompa s Synthesis of Camphoric Acid.— The synthesis of camphoric acid is accomplished by starting with di-ethyl oxalate and condensing it with the di-ethyl ester of di-methyl glutaric acid. 

A synthesis of matrine under milder conditions although in poorer yield has also been reported 106). The ester half-aldehyde of glutaric acid was condensed to the Schiff base CXLVI with aminolupinane. Dehydrogenation conditions caused cyclization with the formation of a mixture which upon reduction yielded matrine, allomatrine, and lup-anine. 

Suppliers General Aniline and Film Corp., Eastern, B, MCB. For the reaction with potassium cyanide, see Glutaric acid for the synthesis of dicyclohexyl ketone, see Scxlium methoxide, condensation catalyst. 

With diethyl malonate. Two different products are obtainable in moderate yield by reaction of malonic ester with formalin. With a 1 2 ratio of aldehyde to ester and diethylamine as catalyst, the product is the tetraester (1), an intermediate in one synthesis of glutaric acid. With a 2 1 ratio and potassium bicarbonate as catalyst, the product is the crystalline solid diethyl bis(hydroxymethyl)malonate (2). ... 

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